Adrenergic receptors are molecules that bind catecholamines. Their activation leads to overall stimulatory and sympathomimetic responses. Learning Objectives Key Points
Key Terms
The adrenergic receptors (or adrenoceptors) are a class of metabotropic G protein -coupled receptors that are targets of the catecholamines, especially norepinephrine or noradrenaline, and epinephrine ( adrenaline ). Although dopamine is a catecholamine, its receptors are in a different category. Many cells possess these receptors, and the binding of an agonist will generally cause a sympathetic (or sympathomimetic) response (e.g., the fight-or-flight response). For instance, the heart rate will increase, pupils will dilate, energy will be mobilized, and blood flow will be diverted from non-essential organs to skeletal muscle. Adrenaline (epinephrine): The 2D structure of adrenaline (epinephrine) is illustrated. Noradrenaline (norepinephrine): The 2D structure of noradrenaline (norepinephrine) is illustrated here. There are two main groups of adrenergic receptors, α and β, with several subtypes. α receptors have the subtypes α1 (a Gq coupled receptor) and α2 (a Gi coupled receptor). Phenylephrine is a selective agonist of the α receptor. β-receptors have the subtypes β1, β2, and β3. All three are linked to Gs proteins (although β2 also couples to Gi), which in turn are linked to adenylate cyclase. Agonist binding thus causes a rise in the intracellular concentration of the second messenger cAMP. Downstream effectors of cAMP include the cAMP-dependent protein, kinase (PKA), which mediates some of the intracellular events following hormone binding. Isoprenaline is a nonselective agonist. Adrenaline or noradrenaline are receptor ligands to α1, α2, or β-adrenergic receptors (the pathway is shown in the following diagram).
Adrenergic signal transduction: This schematic shows the mechanism of adrenergic receptors. Adrenaline and noradrenaline are ligands to α1, α2, or β-adrenergic receptors. α1-receptors couple to Gq, resulting in increased intracellular Ca2+ and causing smooth muscle contraction. α2 receptors couple to Gi, causing a decrease in cAMP activity and resulting in smooth muscle contraction. β-receptors couple to Gs, increasing intracellular cAMP activity and resulting in heart muscle contraction, smooth muscle relaxation, and glycogenolysis. Adrenaline (epinephrine) reacts with both α- and β-adrenoceptors, causing vasoconstriction and vasodilation, respectively. Although α receptors are less sensitive to epinephrine, when activated, they override the vasodilation mediated by β-adrenoceptors. The result is that high levels of circulating epinephrine cause vasoconstriction. At lower levels of circulating epinephrine, β-adrenoceptor stimulation dominates, producing an overall vasodilation. Smooth muscle behavior is variable depending on anatomical location. One important note is the differential effects of increased cAMP in smooth muscle compared to cardiac muscle. Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle. α-receptors have several functions in common, but also individual effects. Common (or still unspecified) effects include: vasoconstriction of cardiac arteries (coronary artery), vasoconstriction of veins, and decreased motility of smooth muscle in the gastrointestinal tract. α1-adrenergic receptors are members of the G protein-coupled receptor superfamily. On activation, a heterotrimeric G protein, Gq, activates phospholipase C (PLC). The PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2), which in turn causes an increase in inositol triphosphate (IP3) and diacylglycerol (DAG). The former interacts with calcium channels of the endoplasmic and sarcoplasmic reticulum, thus changing the calcium content in a cell. This triggers all other effects. Specific actions of the α1-receptor mainly involve smooth muscle contraction. It causes vasoconstriction in many blood vessels, including those of the skin, gastrointestinal system, kidney (renal artery), and brain. Other areas of smooth muscle contraction are:
Further effects include glycogenolysis and gluconeogenesis from adipose tissue and the liver, as well as secretion from sweat glands, and Na+ reabsorption from kidney. Antagonists may be used in hypertension. There are 3 highly homologous subtypes of α2 receptors: α2A, α2Β, and α2C. α2-Receptor Effects
β1-Receptor Effects
β2-Receptor Effects
What happens when norepinephrine binds to beta adrenergic receptors?Norepinephrine binding activates β-adrenergic receptors present on the basolateral membranes of salivary acinar cells. This results in activation of a G-protein that activates adenylate cyclase, which carries out the conversion of ATP to cAMP.
What happens when a beta- Beta 2 Adrenergic Receptor stimulates the Na-K-ATPase pump and moves Potassium into cells and Sodium out of the cells.
Does norepinephrine bind betaNorepinephrine binds to the alpha-1, alpha-2, and beta-1 receptors. Dopamine binds to the alpha-1, alpha-2, beta-1 receptors, and also dopamine receptors.
Which of the following is an effect of norepinephrine?Norepinephrine promotes vasoconstriction, which is a narrowing of the blood vessels. This, in turn, increases blood pressure. Like epinephrine, norepinephrine also stimulates alpha-adrenoreceptors in the cells of the blood vessels. It increases heart rate and blood sugar levels.
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